荷兰重度月经出血女性中子宫内膜消融术联合左炔诺孕酮宫内缓释系统对比单独子宫内膜消融术（MIRA2）：一项多中心、开放标签、随机、对照、优效性试验。
完整摘要 · 中文译文
背景：子宫内膜消融术是治疗月经过多的一种成熟且有效的方法，但许多患者需要进一步治疗，约10%的患者最终在2年内接受子宫切除术。在子宫内膜消融术后立即放置左炔诺孕酮释放宫内系统（LNG-IUS）可能使残留的未处理子宫内膜失活或阻止其再生，从而预防需要子宫切除术的复发症状。本研究旨在评估与单纯子宫内膜消融术相比，月经过多女性在子宫内膜消融术后立即放置LNG-IUS是否能减少2年内后续子宫切除术的需求。 方法：这项多中心、开放标签、随机、对照、优效性试验在荷兰的34家医院进行。纳入年龄小于60岁、患有月经过多且适合接受子宫内膜消融术的女性，并随机分配（1：1）至联合治疗组（子宫内膜消融术加LNG-IUS）或标准治疗组（单纯子宫内膜消融术）（按痛经和年龄分层）。未采用 masking。子宫内膜消融术通过电射频消融或经宫颈子宫内膜切除术完成。分配至联合治疗组的参与者在消融手术后立即进行宫内放置含左炔诺孕酮总量52 mg的LNG-IUS（第一年每日释放20 μg）。主要结局是子宫切除术的发生率 在2年内，基于改良意向性治疗分析，纳入所有有可用数据的参与者。在干预后6周、12个月和24个月时系统评估严重不良事件。本研究已在国际临床试验注册平台注册（NL-OMON54839），且已完成。 结果：2019年11月19日至2023年4月5日期间，715名参与者被随机分配至联合治疗组（n=359）或单纯子宫内膜消融组（n=356）。所有参与者的中位年龄为45岁（IQR 40-48）。42名（6%）参与者在2年随访时主要结局数据缺失。联合治疗组342名参与者中有15名（4%）接受了子宫切除术，而子宫内膜消融组331名参与者中有34名（10%）接受了子宫切除术，对应的相对危险度（RR）为0·43（95% CI 0·24至0·77；p=0·0050），危险差为-0·06（95% CI -0·10至-0·02；p=0·0040）。联合治疗组346名参与者中有27名（8%）报告了严重不良事件，单纯子宫内膜消融组327名参与者中有26名（8%）报告了严重不良事件（RR 0·98，95% CI 0·59-1·65；p=0·94），且无治疗相关死亡。 解读：与单纯子宫内膜消融相比，子宫内膜消融联合左炔诺孕酮宫内缓释系统（LNG-IUS）显著降低了子宫切除术的发生率。联合治疗似乎是月经过多的一种安全辅助策略，不增加并发症风险。 资助：荷兰健康研究与发展组织。
完整摘要 · 英文原文
BACKGROUND: Endometrial ablation is an established and effective treatment for women with heavy menstrual bleeding, but many patients require further treatment, with approximately 10% ultimately undergoing a hysterectomy within 2 years. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation might inactivate residual untreated endometrium or prevent its regeneration, thereby preventing recurrent symptoms necessitating a hysterectomy. The aim of the study was to assess whether LNG-IUS insertion immediately after endometrial ablation in women with heavy menstrual bleeding reduced the need for subsequent hysterectomy within 2 years compared with endometrial ablation alone. METHODS: This multicentre, open-label, randomised, controlled, superiority trial was conducted in 34 hospitals in the Netherlands. Women younger than 60 years with heavy menstrual bleeding who were eligible for endometrial ablation were included and randomly assigned (1:1) to combined treatment comprising endometrial ablation plus LNG-IUS or to standard care comprising endometrial ablation alone (stratified by dysmenorrhoea and age). Masking was not applied. Endometrial ablation was done using electrical radiofrequency ablation or by transcervical resection of the endometrium. In participants allocated to combined treatment, intrauterine insertion of an LNG-IUS containing a total of 52 mg of levonorgestrel (releasing 20 μg per day in the first year) was done immediately after the ablative procedure. The primary outcome was the incidence of hysterectomy within 2 years, analysed on a modified intention-to-treat basis in all participants with available data. Serious adverse events were systematically assessed at 6 weeks, 12 months, and 24 months after the intervention. This study was registered on the International Clinical Trials Registry Platform (NL-OMON54839) and is complete. FINDINGS: Between Nov 19, 2019, and April 5, 2023, 715 participants were randomly assigned to combined treatment (n=359) or endometrial ablation alone (n=356). The median age of all participants was 45 years (IQR 40-48). 42 (6%) participants had missing data for the primary outcome at 2 years of follow-up. A hysterectomy was done in 15 (4%) of 342 participants in the combined treatment group versus 34 (10%) of 331 participants in the endometrial ablation group, corresponding to a relative risk (RR) of 0·43 (95% CI 0·24 to 0·77; p=0·0050), with a risk difference of -0·06 (95% CI -0·10 to -0·02; p=0·0040). Serious adverse events were reported in 27 (8%) of 346 participants in the combined treatment group and 26 (8%) of 327 participants in the endometrial ablation alone group (RR 0·98, 95% CI 0·59-1·65; p=0·94), and there were no treatment-related deaths. INTERPRETATION: The combination of endometrial ablation and LNG-IUS significantly reduced the incidence of hysterectomy compared with endometrial ablation alone. The combined treatment appears to be a safe adjunctive strategy for heavy menstrual bleeding that does not increase the risk of complications. FUNDING: The Netherlands Organization for Health Research and Development.